The objectives of this research are: (1)\to purify a molecule produced by a human hepatoma cell (HHC) line which is able to induce the production of latent collagenase and plasminogen activator (PA) in capillary endothelial cells; and (2)\to relate the ability of this molecule to induce latent collagenase and PA in endothelial cells in vitro to its ability to cause neovascularization in vivo. We have determined that human hepatoma cells produce a molecule which stimulates by 10-\to 50-fold the production of latent collagenase and PA by cultured, primary bovine capillary endothelial (BCE) cells. We hypothesize that the active molecule produced by the hepatoma cells is a physiological inducer of neovascularization. We believe, that during neovascularization in vivo, this molecule stimulates the production of latent collagenase and PA by endothelial cells, thereby inducing two enzymes required for the penetration of new capillaries into surrounding tissues. To test this hypothesis, we will do the following: (1)\purify and characterize the molecule(s) produced by HHC which induces latent collagenase and and PA in BCE cells; (2)\assay the ability of this molecule to induce angiogenesis in vivo; and (3)\establish cultures of human capillary endothelial cells to determine whether the effects of the HHC factor on human cells are comparable to those on BCE cells. (L)